Powder medicine multiple dose administration device

ABSTRACT

A powdered medicine multi-dose administering device in which a hole ( 5   c ) is formed in the bottom surface of a medicine storage chamber ( 5   a ) capable of storing a powdered medicine of an amount of many times of administering operation, the hole ( 5   c ) being located at a position where a pump unit can be communicated with the exterior via a pipe ( 2   g,    2   d ). At the administering position, the powdered medicine in a medicine container unit ( 5   b ) is injected out of the device together with the air through the pipe, while the hole is kept away from being brought into contact with opening means ( 2   f ).

TECHNICAL FIELD

[0001] The present invention relates to a device for feeding a powder ina predetermined amount and a method thereof. More particularly, theinvention relates to a powdered medicine multi-dose administeringdevice.

[0002] More specifically, the invention relates to a powdered medicinemulti-dose administering device by which a powdered medicine of anamount of plural times of administering operation so red in the devicebody is picked up and weighed into a unit dose of powdered medicine of aconstant quantity, which is a very small amount, and is sprayed.

[0003] The invention further provides a relatively inexpensivelyconstructed multi-dose powered medicine administering device by which aunit dose of powdered medicine can be consecutively and precisely pickedup and administered into the body cavity such as the nasal cavity, oralcavity, trachea, bronchus or lung, or into any other diseased part byspraying or inhalation, the device being sanitary, suited to beingcarried and easy to use.

BACKGROUND ART

[0004] Powdered medicine can be administered into a body cavity such asthe nasal cavity, oral cavity or air-way by means of spraying orinhalation. For example, the powdered medicine is administered byspraying into the nasal cavity of a patient suffering from a nasalallergy, or is administered by inhalation into the air-way of a patientsuffering from asthma. For a patient suffering from stomatitis, thepowdered medicine is administered by spraying into the oral cavity.Recently, attention has been given to a drug delivery system in which amedicine is absorbed into the bloodstream through the mucous membrane ofthe nasal cavity or lung, and it has been attempted to administerpowdered medicine via a mucous membrane. Peptide/proteinous drugs suchas insulin and calcitonin, as well as drugs which must exhibit immediateeffect such as migraine-relieving drug and the like drugs have beenproduced in the form of powdery orally administering agents or inhalableagents that can be conveniently used as substitutes for injected drugs,and it has been frequently reported that such drugs are more favorablyabsorbed than the orally administered drugs.

[0005] To administer the powdered medicine, a powdered medicineadministering device is used. Powdered medicine administering devicesare roughly classified into those of the two types according to thesystem for storing the powdered medicine.

[0006] In the first type of powdered medicine administering devices, apowdered medicine in an amount of a unit-dose administration operationis accommodated in the administering device or in an appropriatecontainer such as a capsule. Therefore, a unit dose of powdered medicineis administered at each administering operation. This includes those ofthe disposable type that are discarded after each administeringoperation.

[0007] In the second type of powdered medicine administering devices, apowdered medicine in an amount of many times of administering operationsis accommodated in an appropriate container. Each time an administeringoperation is carried out, a unit dose of powdered medicine is picked upfrom the container and is administered.

[0008] In the present invention, the amount of powdered medicine to beadministered in a single operation is defined as a “unit dose”, and theamount of powdered medicine to be administered in a plurality ofoperations is defined as a “multi-dose”.

[0009] As an example of the powdered medicine unit-dose administeringdevice, Japanese Unexamined Patent Publication (Kokai) No. 59-34267discloses the one which sprays the powdered medicine into the nasalcavity. In these administering devices, in general, a unit dose of thepowdered medicine is contained in a container such as a capsule, andprovision is made of means for piercing the container and air streamintroduction means for spraying the powdered medicine from the containerinto the nasal cavity of a patient. As an example of the disposableunit-dose administering device, International Patent Publication No.2-500172 discloses an administering device which contains a fine powderymedicine, and includes a holding unit forming an opening in the headportion thereof for spraying the medicine so as to be inhaled, and airintroduction means, the bottom of the holding unit being communicatedwith the air introduction means through an air-permeable diaphragm whichdoes not permit the passage of the medicine. Further, WO 97/04826discloses an administering device which is an improvement of the abovedevice.

[0010] Concerning the unit-dose inhaler by which a powdered medicine isinhaled into the air-ways, a large number of devices have been proposed.For example, there is provided an inhaler employing capsules that areusually used pharmacologically. In each capsule, a unit-dose of powderedmedicine is accommodated. Each administering device is provided withmeans for piercing the capsule. After the capsule is pierced, thepowdered medicine is administered by the air flow created by theinhaling action of the user. The administering devices have theirfeatures in the air flow at the time of inhaling and in the state of thecapsule. U.S. Pat. Nos. 3,906,950 and 4,013,075 disclose devices inwhich both ends of the capsule are pierced and the capsule remainsstationary during the inhalation, and U.S. Pat. No. 3,807,400 disclosesthe one in which the capsule moves during the inhalation.

[0011] As an example of the multi-dose administering device, thespecification of WO 94/26338 discloses the one which administers themedicine by spraying. This specification discloses a device comprising astorage chamber detachably attached to the device body and storingmulti-dose of medicine, a container chamber having a capacity ofunit-dose, medicine distribution means movably attached to the devicebody and is communicated at the filling position with the storagechamber and with the container chamber to administer the medicine in thecontainer chamber, and pumping means communicated at the fillingposition with the container chamber to inject the air into the storagechamber to stir up the medicine in the storage chamber, wherein thecontainer chamber is filled with a predetermined amount of powderedmedicine after stirred as it is transferred from the storage chamber bythe sucking force created by the pumping means or by gravity.

[0012] As a nasal cavity administering device, European PatentPublication No. 0744188 discloses a nasal cavity applicator comprising amanual air flow-supplying source for spraying powdered medicine, astorage chamber for storing multi-dose of powdered medicine, a pipe forflowing out the powdered medicine, and means for distributing themulti-dose of powdered medicine into a unit-dose of powdered medicineMeans for distributing the powdered medicine includes a drum-shapedpowdered medicine storage chamber and a rotary sleeve having, on theinside thereof, a plurality of container chambers for containing aunit-dose of medicine.

[0013] As a device for administering the powdered medicine into theair-ways by inhalation, European Patent Publication No. 0211595discloses a device in which a disk-shaped pack is loaded into thedevice, and a series of bubbles are formed around the pack under thecondition that the distances from the bubbles to the center of the packare the same. A predetermined quantity (unit-dose) of powdered medicineis accommodated in these bubbles. This pack is put on the rotarycircular tray about the center axis. The tray has holes at positionscorresponding to the bubbles, and when each bubble is moved to aposition where it is broken by an appropriate opening device, powderedmedicine is taken out from the bubble and is inhaled.

[0014] Further, European Patent Publication No. 0069715 discloses thefollowing device. This administering device includes a containeraccommodating a predetermined quantity of medicine, and a device fortaking out powdered medicine accommodated in the container so as toprepare for the administration of the medicine. The administrationpreparation device is composed of a plate having a predeterminedthickness and a predetermined number of through-holes. The plate iscapable of moving from a position at which the through-holes are partlyfilled with powdered medicine taken out from the container by amechanical means, to a position at which the holes filled with themedicine are located in the passage. When the user inhales through aninhalation port communicated with the passage, the air enters into thepassage, so that the powdered medicine can be taken out from thethrough-hole. There is provided a scraper, which scrapes the powderedmedicine on the container side in the through-hole formed in the plate.According to this specification, the through-holes are completely filledby the action of the scraper. Therefore, a constant dose can be ensured.According to this specification, it is described that the scraper isoptionally provided. However, in order to appropriately operate theinhaler, it is necessary to provide the scraper. The reason is that thedose greatly differs without the scraper. This is because the powderedmedicine in many cases has poor fluidity and it frequently occurs thatthe through-holes are not completely filled with the powdered medicine.

[0015] Though many administering devices have heretofore been contrived,they have their problems as described above.

[0016] When a unit-dose administering device is compared with amulti-dose administering device, the multi-dose administering device ispreferred from the viewpoint of convenience and marketability. This isbecause, in the case of the unit-dose administering device as disclosedin, for example, Japanese Unexamined Patent Publication (Kokai) No.59-34267, a container such as capsule is necessary for containing aunit-dose of medicine and, besides, the device is equipped with meansfor piercing the container. Therefore, the user must mount the containercontaining the powdered medicine and must pierce it according to theinstruction of the administering device. This is never convenient forthe user. The user must carry with him the administering device as wellas the container containing the powdered medicine, which is notconvenient, either. The specification of WO 97/04826 discloses a devicewhich requires a simplified administering operation. In this case,however, the user who needs a plurality of times of administration mustuse an administering device containing a plural number of unit-dosemedicines, accompanied by a problem from the standpoint of portability,The multi-dose administering device is free from the defect related toconvenience inherent in the unit-dose administering device but isaccompanied by another important problem. That is, it is very difficultto consecutively and quantitatively pick up and administer the powderedmedicine in an amount necessary for a unit-dose of administration from alarge amount of the powdered medicine in a collected form, due to achange and deviation in the density of the collected powdered medicine.

[0017] Several contrivances have been made so far to solve theabove-mentioned problem. For example, European Patent Publication No,0069715 mentioned above discloses a method of continuously fillingthrough-holes of a predetermined capacity with the powdered medicinewhile holding the hole with a scraper or the like. Even with thismethod, however, the bulk density of the powdered medicine changes whenthe administering device as a whole is vibrated, whereby thethrough-holes of the predetermined amount are filled with varyingamounts of the medicine; i.e., the medicine is not administered in aconstant amount to the living body. European Patent Publication No.0744188 discloses means for quantitatively dividing the medicine, i.e.,discloses a rotary sleeve equipped with a drum-shaped powdered medicinestorage chamber and a container chamber formed on the inside thereof forcontaining plural unit-dosage medicines. However, the device isrelatively complex, uses a large number of parts which are difficult tomold, and, hence, is expensive.

[0018] Japanese Unexamined Patent Publication (Kokai) No, 3-18376discloses a multi-dose administering device in which a large quantity ofpowdered medicine is compressed, and the compressed body of powderedmedicine is continuously and quantitatively divided and peeled intopieces. According to this method, the powdered medicine is compressed toensure a predetermined quantity of the divided medicine. Even with thismethod, however, when the administering device is vibrated, the bulkdensity of the compressed powdered medicine changes, resulting in achange in the weight of the compressed powdered medicine that is peeledoff. Therefore, the medicine is not administered in a constant amount tothe living body. Further, means for uniformly dividing the powderedmedicine is relatively complex. To put it into clinical use, therefore,problems are involved such as difficulty in the molding and cost ofproduction.

[0019] The specification of WO 94/26338 teaches a multi-doseadministering device in which the air flow passes into the powderedmedicine collected in the storage chamber just prior to the dividingoperation, the medicine in the collected form is moved in space in thestorage chamber to prevent a change in the density of the powderedmedicine and the powdered medicine of an amount of unit-dose iscontained in the powdered medicine container chamber due to the suckingforce and/or gravity, so that the unit-dose of medicine is continuouslyand quantitatively administered after being divided. However, thisdevice includes a storage unit, a medicine container chamber forcontaining medicine of a unit-dose, a medicine-metering means and apumping means and, further, requires a sufficient space for moving thepowdered medicine without causing a change in the density. Thus, as thedevice needs complex parts and is bulky, it is not suited for beingcarried.

[0020] It is desired that the powdered medicine is dispersed intoprimary particles at a moment when the medicine separates away from theadministering device and settles on the administered portion. However,it has been known that the particles cohere during the preservation toform secondary particles; i.e., the particle size distribution shiftstoward a greater side. It is therefore desired that even if the powderedmedicine is cohered in the administering device during the storage, thepowdered medicine is dispersed again into the primary particles At thetime when it leaves the administering device by contriving the structureof the administering device.

[0021] In a system in which the medicine is divided, in a predeterminedvolume, into a unit-dose in the medicine-containing chamber, the weightof the divided medicine undergoes a change when the bulk density of thepowdered medicine changes depending upon the lot of the medicine. It istherefore desired to adjust the weight of the medicine that isadministered depending upon a change in the bulk density of themedicine.

[0022] As described above, none of the conventional powdered medicineadministering devices satisfy the requirements of metering the medicineto be administered, portability by decreasing the size, easyoperability, quick operability, easy production steps, simpleconstituent parts, low cost of production, and a good dispersingproperty of the powdered medicine particles.

DISCLOSURE OF THE INVENTION

[0023] In view of the above-mentioned problems and assignments of theprior art, the present invention provides a powdered medicine multi-doseadministering device that is described below.

[0024] That is, the object of the present invention is to provide apowdered medicine multi-dose administering device which satisfies therequirements of spraying the medicine in a predetermined amount, a smallsize (portability), an easy and quick operation, easy production steps,a dispersion of the powdered medicine, and a decreased number of partsand low cost.

[0025] That is, the present invention is concerned with a powderedmedicine multi-dose administering device comprising:

[0026] means for defining a medicine storage chamber (5 a) capable ofstoring a multi-dose amount of powdered medicine;

[0027] a medicine container unit (5 b) provided under the bottom surfaceof said medicine storage chamber (5 a) and is capable of containing asingle-dose amount of powdered medicine;

[0028] a medicine guiding unit (2) capable of moving between a fillingposition and an administering position while remaining in contact withthe bottom surface of said medicine storage chamber (5 a), and, whenmoved to the filling position, causes said medicine container unit (5 b)to be opened to said medicine storage chamber (5 a) through openingmeans (2 f) and, when moved to the administering position, causes saidmedicine container unit (5 b) to be closed with respect to said medicinestorage chamber (5 a) and causes said medicine container unit (5 b) tobe communicated with the exterior of the device through a pipe (2 g, 2d);

[0029] means (13) communicated with a hole (2 c) formed in the bottomsurface of said medicine storage chamber (5 a) and moves said medicineguiding unit (2) between the filling position and the administeringposition; and

[0030] a pump unit (3) capable of blowing the air into said medicinecontainer unit (5 b) through a filter (6 a) provided in the bottom ofsaid medicine container unit (5 b); wherein

[0031] said medicine guiding unit (2), at the filling position, enablessaid medicine container unit (5 b) to be filled with the powderedmedicine from said medicine storage chamber (5 a) through said openingmeans and, at this moment, said hole (5 c) is located at a positionwhere said pump unit (3) is communicated with the exterior through saidpipe (2 g, 2 d); and

[0032] said medicine guiding unit (2), at the administering position,permits the powdery medicine in said medicine container unit (5 b) to beinjected out of the device together with the air through said pipe (2 g,2 d) while closing said hole (2 c) without joining it to said openingmeans (2 f).

[0033] According to the present invention, the medicine guiding unit canbe easily moved upon being operated from the outer side of the device.When the medicine guiding unit is at the filling position, the powderedmedicine in the powdered medicine storage chamber falls into themedicine container unit through opening means provided in the medicineguiding unit, and is filled therein. When the medicine guiding unitmoves from the filling position to the administering position, thepowdered medicine in the medicine container unit is swept and is meteredinto the amount of one time of administering operation corresponding tothe content of the medicine container unit. Thereafter, the medicinecontainer unit is closed. When the medicine guiding unit further movesto arrive at the administering position, the opening of the pipe of themedicine guiding unit comes into match with the medicine container unit.Upon operating the pump unit, therefore, the air is blown into themedicine container unit, and the powdered medicine in the medicinecontainer unit is ejected, together with the air, out of the devicethrough the pipe.

[0034] The medicine storage chamber and the medicine container unit aremolded integrally together by using a resin to define a body of thedevice. This makes it possible to simplify the structure of the devicebody including the medicine storage chamber and the medicine containerunit, and to easily produce the device body.

[0035] The medicine guiding unit includes a lower disk-like portion anda pole-like portion extending upward from the disk-like portion, whichare integrally molded together using a resin, the opening means is soformed as to penetrate vertically through the disk-like portion, and thepipe is opened at its one end on the lower surface of the disk-likeportion and is opened at its other end in the upper end of the pole-likeportion. The medicine guiding unit is molded as a unitary structureusing a resin. Therefore, the opening means and the pipe work to filland administer the powdered medicine by utilizing the medicine guidingunit.

[0036] The device body is nearly of a cylindrical shape, the disk-likeportion of the medicine guiding unit has a diameter smaller than theinner diameter of the medicine storage chamber of the device body, andthe medicine guiding unit is allowed to rotate between the fillingposition and the administering position over a predetermined angularrange. Therefore, the medicine guiding unit can be changed over betweenthe filling position and the administering position relying simply uponthe rotary operation.

[0037] The device body has a closure unit on the medicine storage unit,the closure unit has a shaft hole at the center thereof for passingthrough the pole-like portion of the medicine guiding unit, and themedicine storage chamber is sealed with the closure unit, medicinestorage unit and medicine guiding unit. Thus, the sealing of themedicine storage chamber is maintained, preventing undesired leakage ofthe powdered medicine.

[0038] The bottom surface of the disk-like portion of the medicineguiding unit comes in contact with the bottom surface of the medicinestorage chamber, the upper and lower positions of the medicine guidingunit are limited by a contact portion formed on the pole-like portion soas to come into contact with the inner surface of the closure unit, andthe bottom surface of the disk-like portion of the medicine guiding unitis brought into intimate contact with the bottom surface of the medicinestorage chamber. This maintains an intimate contact between the bottomsurface of the disk-like portion of the medicine guiding unit and thebottom surface of the medicine storage chamber, to guarantee correctmetering of the powdered medicine and reliable operation.

[0039] The medicine guiding unit has a shaft of a circular shape incross section formed in the upper part of the junction portion of thepole-like portion so as to be fitted to the shaft hole of the closureunit, and has a shaft of a non-circular shape in cross section formed inthe upper part thereof, the means operated from the outer side of thedevice to move the medicine guiding unit between the filling positionand the administering position, is a rotary spray metering change-overdevice which has a non-circular hole that fits to the shaft of anon-circular shape in cross section of the pole portion of the medicineguiding unit, and the medicine guiding unit moves between the fillingposition and the administering position being interlocked to therotational operation of the change-over device. The shaft having thenon-circular shape in cross section and the non-circular hole fittedthereby, have a home base-like pentagonal shape in cross section. Bysimply rotating the rotary spray metering change-over device from theoutside of the device, therefore, the medicine guiding unit can bechanged over between the filling position and the administeringposition, facilitating the operation.

[0040] The rotary spray metering change-over device includes acylindrical portion having a large diameter and a cylindrical portionhaving a small diameter, that are molded integrally together using aresin, the outer periphery of the cylindrical portion having a largediameter forms a rotary operation portion, and the cylindrical portionof a small diameter defines a powdered medicine passage formed therein,has the non-circular hole formed in the base portion, and defines aspray port in an end thereof. The change-over operation is easilyeffected by using the cylindrical portion having a large diameter of thechange-over device, and the cylindrical portion of a small diameterforms a portion of the powdered medicine passage. Accordingly, thepowdered medicine is conveyed up to the spraying port at an end of thedevice, and is sprayed onto the diseased part.

[0041] The rotary spray metering change-over device is formed to bedetachable from the device body and the medicine guiding unit. Thus, thechange-over device can be removed from the device body and from themedicine guiding unit, i.e., can be removed from the administeringdevice itself, can be washed and can be easily reattached to theadministering device.

[0042] A central hole is formed at the center in the bottom surface ofthe disk-like portion of the medicine guiding unit, and a protuberanceis formed at the center on the bottom surface of the medicine storagechamber to work as a shaft that fits to the central hole in order tostabilize the turning of the medicine guiding unit. Accordingly, theturning of the medicine guiding unit is stabilized, and the rotary spraymetering change-over device can be easily turned.

[0043] The rotary spray metering change-over device has an arcuategroove formed in the bottom surface of the cylindrical portion of thelarge diameter with the non-circular hole as a center, the closure unithas a protuberance formed on the upper surface thereof so as to beinserted in the arcuate groove thereby to limit the rotation of themedicine guiding unit and of the rotary spray metering change-overdevice, wherein, when the protuberance is located at an end of thearcuate groove, the position for filling the powdered medicine islimited and, when the protuberance is located at the other end, theposition for administering the powdered medicine is limited.

[0044] The arcuate groove is located in a portion separated away fromthe powdered medicine in the medicine storage chamber, is isolated fromthe passage of the powdered medicine even when it is being sprayed, anddoes not come in contact with the powdered medicine. Namely, the grooveis not clogged with the powdered medicine, and it does not happen thatthe protuberance (4 a) is prevented from freely moving along the groovedue to the clogging of the powder and the powdered medicine is notmetered.

[0045] The closure unit and the medicine storage chamber are secured andintimately adhered together, whereby it is allowed to strictly definethe filling position and the administering position of the powderedmedicine relying upon the protuberance and the arcuate groove.

[0046] On the bottom surface of the disk-like portion of the medicineguiding unit, an angle (x) subtended by the center of the opening meansand the center of the opening of the pipe is from 60 degrees to 180degrees. Further, the angle (y) from one end to the other end of thearcuate groove in the upper surface of the cylindrical portion (13 a).having the large diameter of the rotary spray metering change-overdevice (13) is from 60 degrees to 180 degrees. The angle x and the angley are in such a relationship that they are the same or x is slightlysmaller than y (x≦y).

[0047] The disk-like portion of the medicine guiding unit on the side ofthe medicine storage chamber is inclined upward from the peripherytoward the center at an angle (α) in a range of from 15 degrees to 45degrees with respect to the bottom surface of the disk-like portion.

[0048] The pipe provided in the medicine guiding unit is inclined upwardat angles (β, γ) in a range of from 20 degrees to 70 degrees withrespect to the bottom surface of the medicine guiding unit. The powderedmedicine smoothly flows through the pipe at the time when the powderedmedicine in the medicine container chamber is injected by operating thepump unit.

[0049] The opening means in the medicine guiding unit is a holepenetrating vertically through the disk-like portion.

[0050] The hole extends upward from the opening in the bottom surface ofthe disk-like portion, and expands on the side facing the medicinestorage chamber toward the side of the opening of the pipe thereby toform a pocket-like dent, the dent assisting a smooth conveyance of thepowdered medicine in the medicine storage chamber into the medicinecontainer chamber during the operation for changing over the filling andadministering.

[0051] Here, regarding the size of the dent, the medicine can besmoothly conveyed into the medicine container chamber during theoperation of the rotary spray metering change-over device when the areaof the dent facing the side of the medicine storage chamber is in arange of from 0.1 times to 2.5 times of the opening area and,particularly, from 0.5 times to 1 times of the area of the hole facingthe bottom surface of the disk-like portion. As for the depth of thedent, there is no limitation provided the diameter of the hole remainsunchanged on the side of the medicine container chamber. In practice,due to the difficulty in the molding, the depth of the dent is from 10to 80% and, particularly preferably, 50% of the depth of the hole.

[0052] The dent also decreases the thickness of the disk-like portion ofthe medicine guiding unit. Reduction in the thickness contributes topreventing the contraction or expansion caused by the heat in themedicine guiding unit during the molding, and makes it possible torealize a highly precise spraying performance which is a feature of thepowdered medicine multi-dose administering device.

[0053] One or plural pieces of vanes are formed on the outer side of thepole-like portion of the medicine guiding unit, so that the powderedmedicine in the medicine storage chamber is stirred as the medicineguiding unit moves between the filling position and the administeringposition.

[0054] Here, the vanes possessed by the medicine guiding unit are moldedas a single part using the same material as the medicine guiding unit,and may have any shape or thickness provided they can be molded as asingle part as described above. The angle subtended by the vanes and thecenter line of the medicine passage in the guiding unit may lie over arange of from parallel relation, i.e., from 0 degree to 90 degrees butdesirably lies in a range of from 0 degree to 45 degrees from theviewpoint of accomplishing a high stirring efficiency of the medicine inthe medicine storage chamber during the rotary operation of thechange-over device.

[0055] The pump unit is at least partly constituted by a flexible resinso as to define an air chamber therein, the opening portion of the pumpunit is coupled to the lower part of the device body, the pump unit isdepressed and relaxed to blow the air into the medicine containerchamber through the filter in the air chamber, and the powdered medicineis blown out of the device through the pipe.

[0056] The filter has a recessed portion or a protruded portion on theside facing the medicine container chamber to adjust the volume of themedicine container chamber. In this case, the size of the recessedportion or of the protruded portion of the filter is changed, and thedirection of the filter is changed, to freely change the volume of themedicine container chamber and to adjust the amount of the powderedmedicine administered in one time of administering operation.

[0057] The medicine guiding unit is obtained by molding one or morekinds of high-molecular materials selected from the group consisting ofa polycarbonate, ABS, a high-impact polystyrene and a cyclic olefincopolymer.

[0058] Further, a drying agent is mounted on a portion of the device,the powdered medicine multi-dose administering device is obtained in adisposable type, and it is realized for administration into the bodycavity, into the nasal cavity or into the lung,

BRIEF DESCRIPTION OF THE DRAWINGS

[0059]FIG. 1 is a sectional view illustrating a powdered medicinemulti-dose administering device according to an embodiment of thepresent invention;

[0060]FIG. 2 is a sectional view illustrating a medicine storage unit(5) in a device body (1);

[0061]FIG. 3 is a sectional view illustrating a closure unit (4) in thedevice body (1);

[0062]FIG. 4 is a sectional view illustrating a whole medicine guidingunit (2);

[0063]FIG. 5 is a view illustrating the bottom of the medicine guidingunit (2);

[0064]FIG. 6 is a sectional view illustrating a rotary spray meteringchange-over device (13);

[0065]FIG. 7 is a sectional view illustrating a pump unit (3);

[0066]FIG. 8 is a sectional view illustrating a device cover (9);

[0067]FIG. 9 is a sectional view illustrating a medicine containerchamber (5 b) inclusive of a filter (6);

[0068]FIG. 10 is a view of the filter (6);

[0069]FIG. 11 is a view illustrating near the bottom surface of themedicine guiding unit (2);

[0070]FIG. 12 is a view illustrating near the bottom surface of themedicine guiding unit (2);

[0071]FIG. 13 is a view illustrating near the bottom surface of themedicine guiding unit (2);

[0072]FIG. 14 is a view illustrating near a groove (13 d) of the rotaryspray metering change-over device (13) as viewed from the opposite sideof a cylindrical portion (13 b) of a small diameter;

[0073]FIG. 15 is a diagram of experimental data comparing Example 1 withComparative Example 2, and illustrates a change in the amount ofadministration versus the number of times of injection; and

[0074]FIG. 16 is a diagram of experimental data comparing Example 1 withComparative Example 2, and illustrates a change in the CV value versusthe number of times of injection.

BEST MODE FOR CARRYING OUT THE INVENTION

[0075] The powdered medicine multi-dose administering device(hereinafter often referred to as administering device) of the presentinvention comprises:

[0076] a device body (1) constituted by a closure unit (4) shown in FIG.3 and a medicine storage unit (5) shown in FIG. 2;

[0077] a medicine guiding unit (2) shown in FIG. 4 movably mounted onsaid body (1);

[0078] a rotary spray metering change-over device (13) shown in FIG. 6that rotates being interlocked to the medicine guiding unit (2) and hasa spray port (2 h) at an end thereof;

[0079] a pump unit (3) shown in FIG. 7 of which at least a portion ofthe wall portion that serves as a manual compressed air source forguiding the medicine is constituted by a flexible container or a bag;

[0080] a body cover (9) shown in FIG. 8 for accommodating the spray port(2 h); and

[0081] a filter (6) shown in FIGS. 2, 9 and 10 for partitioning themedicine container chamber (5 b); and

[0082] the present invention further exhibits the following features (I)to (VI):

[0083] (I) the body (1) is constituted by the closure unit (4) and themedicine storage unit (5), the closure unit (4) having a hole (11) atthe center thereof for communicating the medicine guiding unit (2) withsaid body (1), and the interior of a medicine storage chamber (5 a) ishermetically sealed with the closure unit (4), medicine storage unit (5)and said medicine guiding unit (2);

[0084] (II) the medicine storage unit (5) has the medicine storagechamber (5 a) capable of storing the powdered medicine in an amount foradministering the medicine many times, and a medicine container chamber(5 b) formed in the bottom surface of the medicine storage chamber andhaving a content for administering the powdered medicine one time, thefilter (6) being fitted to the bottom surface of the medicine containerchamber (5 b) to permit the passage of the air but inhibiting thepassage of the powdered medicine, the filter serving as an aircommunication port communicated with the pump unit (3) so that the airis blown in upon depressing and relaxing the pump unit (3) at the timeof guiding the medicine;

[0085] (III) the rotary spray metering change-over device (13) having aspray port (2 h) is interlocked to the medicine guiding unit (2)positioned at the center of the body so that they rotate together, therotary spray metering change-over device (13) having, at the centerthereof, a passage (2 c) for passing the powdered medicine and, the airblown out from pump unit (3) through the medicine container chamber (5b) in the device body (1), and capable of being easily detached from thedevice body (1) and the medicine guiding unit (2) for washing;

[0086] (IV) the medicine guiding unit (2) has the passage (2 d) forpassing through the air blown out from the pump unit (3) and for passingthe powdered medicine through the medicine container chamber (5 b) inthe device body (1), and the bottom surface (2 e) of the medicineguiding unit (2) has a disk-like structure of a diameter smaller thanthe inner diameter of the medicine storage unit (5), the bottom surface(2 e) separating the medicine storage chamber (5 a) and the medicinecontainer chamber (5 b) from each other;

[0087] (V) the bottom surface (2 e) of the medicine guiding unit (2)has, in a portion thereof, a hole (2 f) of a diameter larger than thatof the medicine container chamber (5 b) for communicating the medicinestorage chamber (5 a) with said medicine container chamber (5 b), and apipe (2 g) for communicating the medicine container chamber (5 b) withthe passage (2 d) for permitting passage of the powdered medicine andthe air blown out from the pump unit (3) through the medicine-containerchamber (5 b) of the body; and

[0088] (VI) the medicine guiding unit (2) is rotated while beinginterlocked to the rotary spray metering change-over device (13) tobring the hole (2 f) in the bottom surface (2 e) of the medicine guidingunit (2) into agreement with the medicine container chamber (5 b) of inthe device body (1), the medicine storage chamber (5 a) is communicatedwith the medicine container chamber (5 b) so that the medicine containerchamber (5 b) is filled with the powdered medicine from the medicinestorage chamber (5 a), and the medicine guiding unit (2) is rotatedwhile being interlocked to the rotary spray metering change-over device(13) whereby the bottom surface (2 e) of the medicine guiding unit (2)sweeps the powdered medicine in the medicine container chamber (5 b) sothat the powdered medicine, in a predetermined amount, is contained inthe medicine container chamber (5 b) and, then, the medicine guidingunit (2) is rotated while being interlocked to the rotary spray meteringchange-over device (13), whereby the medicine container chamber (5 b),pipe (2 g), passage (2 d) and spray port (2 h) are communicated with oneanother, and the air is blown out from the pump unit (3), and thepowdered medicine weighed into a predetermined amount is sprayed fromthe spray port (2 h) of the rotary spray metering change-over device(13).

[0089] The administering device of the present invention can beassembled in a manner as described below.

[0090] First, the filter (6) is set in position by being pushed from theouter side into the medicine container chamber (5 b) formed in thebottom on the outer side of the device body (1). The setting position isdefined by forming a step in the medicine container chamber (5 b) at thetime of molding the device body (1). Then, the medicine guiding unit (2)is inserted in the medicine storage unit (5) at such a position that,for example, the medicine container chamber (5 b) is in agreement withthe hole (2 f) formed in the medicine guiding unit (2) and having adiameter larger than that of the medicine container chamber, and thehole (14) at the center of the bottom surface (2 e) of the medicineguiding unit (2) is fitted and secured to the protuberance (8) at thecenter of the bottom surface of the device body. Here, the requiredamount of powdered medicine is introduced into the medicine storagechamber (5 a) in the device body (1). Then, the closure (4) isintimately adhered and secured to the device body (1) while passing theguiding unit (2) through the hole (11) at the center. Next, the rotaryspray metering change-over device (13) having a spray port (2 h) issecured to the device body (1) in a manner that the shaft (2 k) of anon-circular shape in cross section at the end of the guiding unit (2)is brought into agreement with the non-circular hole (13 c) in theguiding unit of the rotary spray metering change-over device (13). It isdesired that the shaft (2 k) and the non-circular hole (13 c) have ahome base-like pentagonal shape in cross section having two parallelsides for exclusively determining their rotational positions, a side atright angles thereto and two sides on the opposite sides. During theassembling, the protuberance (4 a) of the closure (4) is inserted in oneend of an arcuate hole (13 d) in the bottom surface of the rotary spraymetering change-over device (13). Next, the pump unit (3) is connectedand secured to the lower part of the device body (1) and, finally, thebody cover is connected to the device body (1) so as to cover the sprayport (2 h) to thereby complete the administering device of theinvention.

[0091] Next, described below are the materials constituting the parts ofthe present invention.

[0092] It is desired that the device body (1), medicine guiding unit(2), rotary spray metering change-over device (13), closure (4) and bodycover (9) are usually obtained by molding one or more kinds of polymersselected from the group consisting of polyethylene, polystyrene,polypropylene, styrene/acrylonitrile polymer (AS),acrylonitrile/butadiene/styrene polymer (ABS), polycarbonate,high-impact polystyrene and cyclic polyolefin copolymer, to which only,however, they are in no way limited.

[0093] Among them, it is desired that the medicine guiding unit (2) isobtained by molding one or more polymers selected from the groupconsisting of acrylonitrile/butadiene/styrene polymer (ABS),polycarbonate, high-impact polystyrene and cyclic polyolefin copolymerin order to heighten the intimate adhesion between the medicine guidingunit (2) and the device body (1).

[0094] As the filter (6) provided at an end of the medicine containerchamber (5 b) of the invention, there can be suitably used a sievingmesh or a membrane filter depending upon the size of particles of themedicine and the excipient (which may not always be used) constitutingthe powdered medicine. When used for spraying the medicine into thenasal cavity, there is used a sieving mesh having a size of opening offrom 0.5 to 38 μm and, more preferably, from 1 to 25 μm, or a membranefilter having a porous diameter of from 5 to 75 μm, and more preferably,from 5 to 25 μm. When used for spraying the medicine into the air-ways,there is used a membrane filter having a size of opening of not largerthan 1 μm. The sieving mesh may be made of a nylon or a stainless steel,and the membrane filter may be made of a polyethylene, polypropylene,cotton, rayon, glass fiber or may be a sintered filter.

[0095] It is also allowable to attach the filter even into the hole (5c) in the bottom surface of the medicine storage chamber (5 a).

[0096] The pump unit (3) of the invention is an element for compressingthe air to administer the powdered medicine (by spraying or inhalation).It is desired that at least a portion of the flexible member or of thewall of the pump is made of a flexible material. Here, at least aportion is made of a flexible material means that upon pushing andrelaxing a portion made of the flexible material, the powdered medicinecontained in the medicine container chamber (5 b) can be sprayed orinhaled. This includes the cases where the whole pump unit (3) isconstituted by the flexible material, and where the pump unit (3) isconstituted by the flexible material except a portion near the junctionportion to the device body (1) and other portions are constituted by thenon-flexible material.

[0097] As such a flexible material, there can be used a plastic havingelasticity such as polyethylene or polypropylene, and a natural or asynthetic rubber.

[0098] The powdered medicine used in the present invention can beconstituted by, for-example, a medicine and a widely known excipientsuch as milk sugar, starches, celluloses or polyvinyl polymer, or may beconstituted by a medicine alone. As required, further, the powderedmedicine may be suitably blended with known additives such asstabilizers, antioxidants or the like.

[0099] As the medicine to be used for the invention, there can be used awide range of medicines. Concrete examples includenon-peptide/proteinaceous drugs such as steroidal anti-inflammatorydrugs or non-steroidal anti-inflammatory drugs, analgesicsanti-inflammatory drugs, antimuscarinics, antidepressants, coughsuppressants expectorants mucolytics, anti-histamic agents,anti-allergic agents, nausea-suppressing agents, anti-insomnia drugs,vitamins, sex hormones, anti-neoplastics, anti-arrhythmias, hypertensiondrugs, anxyiolytic sedatives, anti-psychotics, anti-gastric ulcer drugs,heart failure treating drugs, analgesics, bronchodilators, obesitytreating agents, platelet coaggregation suppressing agents,anti-diabetics, muscle-relaxants, anti-migraines and anti-rheumatoidarthritis drugs. There can be further used peptide/proteinaceous drugssuch as hormones, cytocains, vaccines, as well as nuclear acids such asanti-sense and genes.

[0100] As the non-peptide/proteinaceous medicines, there can be usedthose of one or two or more kinds of the drugs selected from theabove-mentioned group. Among them, there can be preferably used one ortwo or more of those selected from the group consisting ofnausea-suppressing agent, anti-insomnia drugs, vitamins, sex hormones,anti-migraines and analgesics.

[0101] As the non-peptide/proteinaceous drugs, there can be exemplifiedone or two or more kinds of non-peptide/proteinaceous drugs selectedfrom the group consisting of steroidal anti-inflammatory drugs ornon-steroidal anti-inflammatory drugs, such as hydrocortisone,predonisolone, triamcinolone, dexamethasone, betamethasone,becromethasone, fluticasone, momethasone, fluocortine, budesonide,salbutamol, and salmeterol; analgesics anti-inflamatory drugs such asacetoaminophene, phenacetin, aspirin, aminopirin, sulpirin,phenylbutazone, mefenamic acid, fulfenamic acid, ibufenac, ibuprofen,alchlofenac, dichlofenac and indomethacin; antimuscarinics such asscopolamine; antidepressants such as imipramine; cough suppressantsexpectorants mucolytics such as sodium chlomoglicate, codeine phosphateand isoproterenol hydrochloride; anti-histamic agents such asdiphenehydramine, triprolydine, isothipendyl, and chlorophenylamine;anti-allergic agents such as amlexanox, azelastin, ozagrel, tranilastand ketotifen; nausea-suppressing drugs such as ondansetron,granisetron, metoclopramide, cisapride, domperidone; anti-insomnia drugssuch as brotizolam and melatonin; vitamins such as cyanocobalamin,mecobalamine; sex hormones such as estradiol, estriol, progesterone, andtestosterone; anti-neoplastics such as tamoxifen and tegafur;anti-arrhythmias such as propranolol, atenolol; hypertension drugs suchas nicaldipine; anxyiolytic sedatives such as diazepam; anti-psychoticssuch as nitrazepam; anti gastric ulcer drugs such as cimetidine andranitidine; heart failure treating drugs such as dopamine; analgesicssuch as morphine and buprenorphine; bronchodilators such as oxytropiumand ozagrel; obesity-treating drugs such as mazindol; plateletcoaggregation suppressing agents such as beraprost and carbacyclin;anti-diabetics such as acarbose and sorbinil; muscle relaxants such aspinaberium and inaperizon; anti-migraines such as ergotamine, imigranand alniditan; and anti-rheumatoid arthritis drugs such as actarit andplatonin.

[0102] As the pep tideproteinaceous drugs, there can be exemplifiedhormones and cytocains such as lutenising hormone-releasing hormones,growth hormone-releasing factors, somatostatin derivatives,vasopressins, oxytocins, hirudin derivatives, enkephalins,adrenocorticotropic hormone derivatives, bradikinin derivatives,carcitonins, insulins, glucagon derivatives, growth hormones, growthhormone-releasing hormones, lutenising hormones, insulin-growingfactors, calcitonin gene-related peptides, atrium sodium urinationpeptide derivatives, parathyroid hormones, parathyroid hormone-releasinghormones, prolactin, thyroid stimulating hormone-releasing hormones,angiotensins, interferons, interleukins, erythropoietint granulocytecolony stimulating factor, and microphage formation-stimulating factor.As the peptide/protenaceous drugs, those selected from theabove-mentioned group can be used in one, two or more kinds.

[0103] As the vaccines, there can be exemplified whooping cough vaccine,diphtheria vaccine, tetanus vaccine and influenza vaccine.

[0104] Described below are the sizes and volumes of the constituentparts of the invention.

[0105] The medicine storage unit (5) which is an internal space of thedevice body (1) of the invention has a volume as small as possible tooffer good operability. More specifically, they are determined by theprotuberance (8) on the bottom surface in the medicine storage unit (5),sizes of the opening of the medicine container chamber (5 b) and of themedicine guiding unit (2), size of the pump unit (3) to be connected andthe method of its connection, size of the operating portion of therotary spray metering change-over device (13) (portion for turning therotary spray metering change-over device (13) by hand) and the amount ofthe medicine that is stored.

[0106] The amount of the medicine to be stored in the administeringdevice of the invention varies depending Upon the kind of the medicine.When, for example, the powdered medicine is to be administered into thetwo nasal cavities two times a day in an amount of 15 mg each time perone cavity (i.e., four times a day), then, the amount (weight) of thepowdered medicine to be stored for two weeks use becomes 15×4×14=840 mg,If the powdered medicine has a bulk density of 0.6, then, the volume is1.4 ml, Therefore, if the device body (1) has a depth of 25 mm and adiameter of 16 mm to maintain a volume of about 5 ml, then, there isrealized a small administering device capable of storing the medicine ina sufficient amount even by taking the junction portion (10) between themedicine guiding unit (2) contained therein and the closure unit (4)into consideration.

[0107] Further, the volume of the medicine container chamber (5 b) inthe device body (1) can be suitably determined depending upon-the volumeof the powdered medicine used in each administering operation and thenumber of times of administering operation. When the powdered medicinethat is usually used has an apparent specific gravity of about 0.1 to3.0 and the powdered medicine is used in an amount of about 5 to 200 mgeach time, then, the medicine container chamber (5 b) must have a volumeof about 2 to 2000 mm³.

[0108] The volume of the medibine container chamber (5 b) can beadjusted by providing the filter (6) with a protruded portion (6 a) of adissimilar volume. By adjusting the length (volume) of the protrudedportion (6 a) depending upon the bulk density of the powdered medicine,it is allowed to adjust the weight of the medicine that is metered andpicked up depending upon a change in the bulk density of the powderedmedicine. Though there is no particular limitation in the shape of theprotruded portion, there can be exemplified a conical shape or acylindrical shape.

[0109] It is desired that the pump unit (3) of the invention is capableof blowing the air in such amounts that the powdered medicine containedin the medicine container chamber (5 b) is almost all discharged upondepressing the pump unit (3) one or several times to ten times.

[0110] The invention will be described in further detail.

[0111] According to the administering device of the invention, themedicine in the medicine storage chamber (5 a) is contained in themedicine container chamber (5 b) by turning the medicine guiding unit(2) being interlocked to the rotary spray metering change-over device(13), and the unit-dose of medicine is swept by turning the medicineguiding unit (2) in the reverse direction so as to be contained in themedicine container chamber (5 b). Thus, the unit-dose of medicine can beeasily and correctly picked up and metered from the powdered medicine ofa multi-dose amount stored in the medicine storage chamber (5 a) withoutusing any particular device such as scraper and without using any meansfor preventing a change in the density by passing the air to cope with achange or deviation in the bulk density of the powdered medicine thatmay occur during the preservation. Here;

[0112] (a) since the closure unit (4) is mounted on the device body (1),the medicine guiding unit (2) is brought into intimate contact with themedicine storage chamber (5 a) and no medicine leaks through the gapbetween the medicine guiding unit (2) and the medicine storage chamber(5 a) and, besides, the powdered medicine does not change its physicalproperties because the interior of the medicine storage chamber (5 a)has been hermetically sealed;

[0113] (b) the medicine guiding unit (2) is turned in an intimatelyadhered state mentioned in (a) above involving a slight degree ofresistance to impart a suitable degree of vibration to the powderedmedicine and to prevent a change in the density of the powderedmedicine;

[0114] (c) the hole (2 f) formed in the bottom surface (2 e) of themedicine guiding unit (2) for connecting the medicine storage chamber (5a) with the medicine container chamber (5 b), has a diameter larger thanthat of the medicine container chamber (5 b), enabling the medicine tobe reliably contained in the medicine container chamber (5 b);

[0115] (d) the hole (2 c) formed in the bottom surface of 0 the medicinestorage unit (5) comes into agreement with the pipe (2 g) opened in thebottom surface (2 c) of the medicine guiding unit (2), whereby a greatlydecreased pressure is applied into the medicine container chamber (5 b)from the pump (3) at the time of filling the medicine, and the powderedmedicine is filled very accurately; and

[0116] (e) the surface (2 i) of the medicine guiding unit (2) on theside of the medicine storage chamber (5 a) is inclined by an angle (α)relative to the bottom surface (2 e) of the medicine guiding unit (2) toimpart suitable degree of vibration and motion to the powder to increaseits fluidity when the medicine guiding unit (2) rotates, so that themedicine is reliably contained in the medicine container chamber (5 b);

[0117] thus making it possible to make uniform the amount of thepowdered medicine contained in the medicine container chamber (5 b).

[0118] In the administering device of the invention, a decrease in thenumber of the parts contributes to minimizing the size of the wholedevice. Besides, the passage (2 d) that is installed along the axis ofthe medicine guiding unit (2) contributes to minimizing the size(height) of the administering device as a whole, so that it can beeasily carried.

[0119] The administering device of the present invention has the arcuatehole (13 d) formed in the bottom surface of the cylindrical portion of alarge diameter of the rotary spray metering change-over device (13) withthe non-circular hole as a center, has the protuberance (4 a) on theupper surface of the closure unit (4) so as to be inserted in thearcuate hole (13 d), whereby when the rotary spray metering change-overdevice (13) is rotated causing the protuberance (4 a) to arrive at anextreme end of the hole (13 d), there is established the fillingposition at where the hole (2 f) in the bottom surface (2 e) of themedicine guiding unit (2) is superposed on the medicine containerchamber (5 b) of the device body (1) enabling the medicine containerchamber (5 b) to be filled with the powdered medicine and, besides, whenthe hole (5 c) in the bottom surface of the medicine storage unit (5) isbrought into agreement with the pipe (2 g) of the medicine guiding unit(2), the interior of the pump (3) is communicated with the exterior ofthe administration device, so that a decreased pneumatic pressure isapplied into the medicine container chamber (5 b) from the pump (3) andthat the powdered medicine is filled maintaining a high accuracy. Whenthe protuberance arrives at the extreme end of the arcuate hole (13 d)on the opposite side, the pipe (2 g) of the medicine guiding unit (2) isconnected to the medicine container chamber (5 b), and the powderymedicine in the medicine container chamber (5 b) becomes ready to besprayed with an easy operation. When a charging position is marked at anend of the turn of the rotary spray metering change-over device (13) atwhere the medicine is filled and the other end is marked as a sprayingposition, then, the device can be more easily operated while preventingerroneous operation.

[0120] In the administering device of the present invention as describedabove, the medicine storage unit (5) is combined with the medicineguiding unit (2) and with the closure unit (4) to establish ahermetically sealed state in the medicine storage chamber 5 a. Due tothe hermetically sealed state, however, a difference occurs in thepneumatic pressure among the medicine storage chamber (5 a), the pump(3) and the exterior of the administering device at the time of fillingthe medicine.

[0121] In the administering device of the present invention, however,the hole (5 c) is formed in the bottom surface of the medicine storagechamber (5 a), and is brought into agreement with the pipe (2 g) openedin the bottom surface of the medicine guiding unit at the time offilling the medicine, enabling the pneumatic pressure to become uniformamong the medicine storage chamber (5 a), pump (3) and exterior of theadministering device. Therefore, a predetermined amount of the medicinecan be metered.

[0122] Referring to FIG. 5, it is desired that the angle (x) subtendedby the center of the pipe (2 g) and the center of the hole (2 f) formedin the bottom surface (2 e) of the medicine guiding unit (2), is equalto the angle (y) of the arcuate hole (13 d) in the rotary spray meteringchange-over device 13 shown in FIG. 14, and is in a range of from 60degrees to 180 degrees and, more preferably, from 90 degrees to 120degrees. While the medicine guiding unit (2) rotates between the fillingposition and the administering position within the above range ofangles, the vanes (21) provided in a number of 2 to 3 in the axialdirection work to stir the medicine in the medicine storage chamber (5a).

[0123] It is desired that the surface (2 i) of the medicine guiding unit(2) on the side of the medicine storage chamber (5 a) has an angle (α)over a range of from 15 degrees to 45 degrees with respect to the bottomsurface (2 e) of the medicine guiding unit (2) from the standpoint ofmetering the medicine. More preferably, the angle is in a range of from25 degrees to 35 degrees. It is further desired that the pipe (2 g) ofthe medicine guiding unit (2) has angles (β, γ) over a range of from 20degrees to 60 degrees with respect to the bottom surface (2 e) of themedicine guiding unit (2) from the standpoint of dispersing themedicine, More preferably, the angles (β, γ) are in a range of from 25degrees to 40 degrees.

[0124] The administering device of the invention may be furnished with adrying agent that is usually used to avoid a change in the bulk densityof the powdered medicine caused by the humidity and to maintaindispersing property of the medicine when it is sprayed.

[0125] The administering device of the present invention may bedisposable.

[0126] Though there is no particular limitation on the portions to wherethe powdered medicine can be administered by using the administeringdevice of the invention, the medicine can be administered into bodycavities such as a nasal cavity or the lungs.

[0127] The present invention provides a relatively inexpensivelyconstructed powdered medicine multi-dose administering device which isconvenient to carry, easy to use, and is capable of correctlyadministering the powdered medicine by spraying or inhalation, which isan excellent effect.

[0128] The invention is adapted as an administering device containing,in the container, multi-dose amount of the powdered medicine which isadministered in a very small amount in each administering operation.

EXAMPLES

[0129] The invention will now be described by way of examples withreference to the accompanying drawings. It should, however, be notedthat the invention is in no way limited thereto only.

[Example 1]

[0130]FIG. 1 is a sectional view illustrating the entire constitution ofthe multi-dose powdered medicine administering device according to thepresent invention. The device body (1) of a cylindrical shape wasobtained by molding a cyclic olefin copolymer, the device body (1)having a medicine storage chamber (5) of an inner diameter of 15 mm andhaving a medicine container chamber (5 b) of a diameter of 3.5 mm and adepth of 3.3 mm. In the bottom surface of the medicine storage unit,there were formed a medicine container chamber (5 b) and a hole (5 c)having diameters of 3 mm and 2 mm, respectively. Further, the rotaryspray metering change-over device (13) was obtained by molding apolypropylene, the rotary spray metering change-over device (13) havinga spray port (2 h) of a diameter of 4 mm and having a bottom portion ofan inner diameter of 18 mm for connection to the closure unit (4) and tothe device body (1). The medicine guiding unit (2) was obtained bymolding a cyclic olefin copolymer and was mounted on the device body,the medicine guiding unit (2) having the shape of a disk with a bottomsurface of a diameter of 15 mm and a pole of a height of 27.5 mmconnected to the rotary spray metering change-over device (13). In themedicine guiding unit (2), the angle (x) subtended by the center of thehole (2 f) and the center of the pipe (2 g) was set to be 115 degrees tobe corresponded to the angle (y) of the arcuate hole (5 c) formed in thebottom surface of the medicine storage unit (5). The angle (α) of theinclined surface (2 i) to the bottom surface (2 e) was 30 degrees, andthe angles of the pipe (2 g) were 35 degrees (β) with respect to thebottom surface (2 e) on the outer side and 40 degrees (y) with respectto the bottom surface (2 e) on the inner side. Further, the closure unit(4) shown in FIG. 3 was obtained by molding a polyropylene, the closureunit (4) having a hole (11) of a diameter of 5.0 mm in which an end (2j) of the medicine guiding unit (2) was inserted. Next, the device body(1) was equipped with a membrane filter (6) made of a polypropylenehaving an opening size of 5 μm and with a pump unit (3) made ofpolyethylene. The medicine storage unit (5) was filled with 1000 mg ofthe powdered medicine having a particle diameter of 38 to 150 μm. Theclosure unit (4) was inserted in the device body (1), the rotary spraymetering change-over device (13) was mounted on the main body (1) and,finally, the spray port (2 h) was covered with a device cover (9) madeof polypropylene to complete the administering device of the invention(the whole device having a height of about 85 mm and a diameter of about24 mm).

[Comparative Example 1]

[0131] In Example 1, the device body (1) and the medicine guiding unit(2) were obtained by molding the cyclic olefin copolymer. In ComparativeExample 1, however, these two parts were obtained by molding apolypropylene, and the others were the same as those of Example 1. Onegram of a mixture powder (bulk density=0.50) of a hydroxypropylcellulose (99.8%) having a particle size of 49 to 150 microns andmagnesium stearate (0.2%) was introduced into the medicine storage units(5) of these Example 1 and Comparative Example 1. The rotary spraymetering change-over device (13) was reciprocally moved between thefilling position and the spraying position, and the pump was depressedat the spraying position to consecutively spray the mixture powder. Thetotal weight of the administering device was measured each time torecord the spraying amount of unit-dose. After sprayed 30 times. Example1 offered a very stable and constant spraying amount of 16.7 ag (CV2.2%) in average, and permitted the rotary spray metering change-overdevice (13) to smoothly rotate reciprocally without any problem. In theComparative Example 1, the spraying amount was 16.0 mg (CV=2.8%) inaverage which was as uniform as that of Example 1. After about twentiethadministering operation, however, resistance was involved in thereciprocal motion of the rotary spray metering change-over device (13).When left to stand one day after the thirtieth administering operation,the rotary spray metering change-over device (13) did not almost rotate.Further, the mixture powder was found between the bottom surface in thedevice body and the medicine guiding unit (2). From this fact, it waspresumed that an error was occurring in the sizes of the device body (1)and in the medicine guiding unit (2) of Comparative Example 1 due to thehigh-molecular material used for the molding.

[Comparative Example 2]

[0132] In Comparative Example 2, the device body was obtained by usingthe same materials as those of Example 1 and in the same manner as inExample 1 but without forming the hole (5 c) in the bottom surface ofthe medicine storage unit (5). One gram of a mixture powder (bulkdensity=0.50) of a hydroxypropyl cellulose (99.8%) having a particlesize of 49 to 150 microns same as those of the above Comparative Example1 and magnesium stearate (0.2%) was introduced into the medicine storageunits (5) of these Example 1 and Comparative Example 2. The rotary spraymetering change-over device (13) was reciprocally moved between thefilling position and the spraying position, and the pump was depressedat the spraying position to consecutively spray the mixture powder. Thetotal weight of the administering device was measured each time torecord the spraying amount of unit-dose. The results were as shown inTable 1 and in FIGS. 15 and 16. After sprayed 30 times, Example 1offered a very stable and constant spraying amount of 16.7 mg (CV=2.2%)in average, and permitted the rotary spray metering change-over device(13) to smoothly rotate reciprocally without any problem. In theComparative Example 2, the spraying amount was 15.8 mg (Cv=2.8%) inaverage which was a slight decrease in the uniformity of spraying ascompared to Example 1, but was within a medicinally allowable range interms of spraying accuracy. The same devices were filled with the samepowder in the same amount to make sure the reproduceability. in Example1, the spraying amount was very stable and was as uniform as 16.5 mg(Cv=1.9%), and almost no difference was recognized from the first time.Besides, the rotary spray metering change-over device (13) smoothlymoved reciprocally without problem. in Comparative Example 2, on theother hand, the spraying amount was 14.1 mg (CV=10.5%) indicating a dropin the uniformity of spraying as compared to that of Example 1. Besides,the average spraying amount has dropped by more than 1 mg compared tothat of the first time of Comparative Example 1, and the CV valueincreased, too. TABLE 1 Data comparing Example 1 with ComparativeExample 2 Comparative Example 2 Example 1 Accmltd Accmltd Accmltd admstdAccmltd admstd Ave. Admstd Admstd admstd amount Ave. Admstd Admstdadmstd amount admstd amount amount amount (%) to admstd amount amountamount (%) to Admstd amount from from from total Admstd amount from fromfrom total amount from 1st time 1st time 1st time amount amount from 1sttime 1st time 1st time amount Time (mg) 1st time (SO) (CV %) (mg) filled(mg) 1st time (SO) (CV %) (mg) filled 1 13.6 13.60 #DIV/O! #DIV/O! 13.601.24 15.0 15.00 #DIV/O! #DIV/O! 15.00 1.36 2 13.7 13.65 0.07 0.52 27.302.48 14.9 14.95 0.07 0.47 15.00 2.72 3 13.6 13.63 0.06 0.42 40.90 3.7214.9 14.93 0.06 0.39 29.90 4.07 4 14.0 13.73 0.19 1.36 54.90 4.99 15.215.00 0.14 0.94 44.80 5.45 5 14.0 13.78 0.20 1.49 68.90 6.26 15.2 15.040.15 1.01 60.00 6.84 6 14.5 13.90 0.35 2.49 83.40 7.58 15.2 15.07 0.151.00 75.20 8.22 7 14.2 13.94 0.34 2.41 97.60 8.87 15.1 15.07 0.14 0.9290.40 9.59 8 13.9 13.94 0.31 2.23 111.50 10.14 14.9 15.05 0.14 0.94105.50 10.95 9 14.6 14.01 0.37 2.61 126.10 11.46 13.1 15.06 0.13 0.89120.40 12.32 10 14.1 14.02 0.35 2.47 140.20 12.75 14.9 15.04 0.13 0.90135.50 13.67 11 14.1 14.03 0.33 2.34 154.30 14.03 14.9 15.03 0.13 0.90150.40 15.03 12 13.8 14.01 0.32 2.29 168.10 15.28 14.9 15.02 0.13 0.89165.30 16.38 13 13.7 13.98 0.32 2.28 181.80 16.53 15.3 15.04 0.15 1.00180.20 17.77 14 14.2 14.00 0.31 2.22 196.00 17.82 14.8 15.02 0.16 1.05195.50 19.12 15 13.3 13.95 0.35 2.51 209.30 19.03 15.1 15.03 0.15 1.02210.30 20.49 16 13.5 13.93 0.36 2.56 222.80 20.25 15.0 15.03 0.15 0.99225.40 21.85 17 14.0 13.93 0.35 2.48 236.80 21.53 14.9 15.02 0.15 0.98240.40 23.21 18 13.2 13.89 0.38 2.72 250.00 22.73 15.0 15.02 0.14 0.95270.30 24.57 19 14.2 13.91 0.37 2.69 264.20 24.02 14.8 15.01 0.15 0.98285.10 25.92 20 14.0 13.91 0.36 2.62 278.20 25.29 14.7 14.99 0.16 1.06299.80 27.25 21 12.9 13.86 0.42 3.01 291.10 26.46 15.2 15.00 0.16 1.07315.00 28.64 22 13.6 13.85 0.41 2.97 304.70 27.70 15.1 15.00 0.16 1.06330.10 30.01 23 13.0 13.81 0.44 3.18 317.70 28.88 14.8 15.00 0.16 1.07344.90 31.35 24 13.1 13.78 0.45 3.29 330.80 30.07 14.9 14.99 0.16 1.06359.80 32.71 25 12.7 13.74 0.49 3.60 343.50 31.23 14.8 14.98 0.16 1.07374.60 34.05 26 14.0 13.75 0.49 3.54 357.50 32.50 14.9 14.98 0.16 1.05389.50 35.41 27 12.5 13.70 0.53 3.90 370.00 33.64 15.0 14.98 0.15 1.03404.50 36.77 28 12.4 13.66 0.58 4.24 382.40 34.76 14.8 14.98 0.16 1.04419.30 38.12 29 12.8 13.63 0.59 4.34 395.20 35.93 15.0 14.98 0.15 1.02434.30 39.48 30 13.8 13.63 0.58 4.27 409.00 37.18 15.0 14.98 0.15 1.00449.30 40.85 31 12.6 13.60 0.60 4.42 421.60 38.33 14.9 14.97 0.15 0.99464.20 42.20 32 13.8 13.61 0.59 4.35 435.40 39.58 15.2 14.98 0.15 1.01479.40 43.58 33 10.8 13.52 0.76 5.63 446.20 40.56 14.8 14.98 0.15 1.02494.20 44.93 34 10.7 13.44 0.89 6.64 456.90 41.54 15.1 14.98 0.15 1.01509.30 46.30 35 13.0 13.43 0.88 6.57 469.90 42.72 14.8 14.97 0.15 1.02524.10 47.65 36 12.9 13.41 0.87 6.51 482.80 43.89 15.2 14.98 0.15 1.03539.30 49.03 37 11.3 13.35 0.93 6.95 494.10 44.92 14.8 14.98 0.16 1.04554.10 50.37 38 11.0 13.29 0.99 7.46 505.10 45.92 14.9 14.97 0.15 1.03569.00 51.73 39 14.5 13.32 1.00 7.49 519.60 47.24 14.8 14.97 0.15 1.03583.80 53.07 40 10.8 13.26 1.06 8.02 530.40 48.22 14.7 14.96 0.16 1.06598.50 54.41 41 14.9 14.96 0.16 1.04 613.40 55.76 42 14.9 14.96 0.151.03 628.30 57.12 43 14.9 14.96 0.15 1.02 643.20 58.47 44 14.9 14.960.15 1.01 658.10 59.83 45 15.1 14.96 0.15 1.01 673.20 61.20 46 14.914.96 0.15 1.00 688.10 62.55 47 14.7 14.95 0.15 1.02 702.80 63.89 4815.1 14.96 0.15 1.02 717.90 65.26 49 14.9 14.96 0.15 1.01 732.80 66.6250 15.0 14.93 0.15 1.01 747.80 67.98 51 14.9 14.95 0.15 0.99 762.7069.34 52 15.1 14.96 0.15 0.99 777.80 70.71 53 15.0 14.96 0.15 0.98552.40 50.22 54 14.7 14.95 0.15 1.00 807.50 73.41 55 14.7 14.95 0.151.02 822.20 74.75 56 15.2 14.95 0.15 1.04 837.40 76.13 57 14.8 14.950.15 1.04 852.20 77.47 59 14.5 14.94 0.16 1.00 866.70 78.79 59 14.614.94 0.17 1.13 881.30 80.12 60 15.1 14.94 0.17 1.13 896.40 81.49 6115.1 14.94 0.17 1.13 911.50 82.86 62 14.9 14.94 0.17 1.12 926.40 84.2263 14.8 14.94 0.17 1.12 941.20 85.56 64 14.8 14.94 0.17 1.12 956.0086.91 65 14.1 14.92 0.20 1.31 970.10 88.19 66 14.5 14.92 0.20 1.35565.30 51.39 67 14.5 14.91 0.21 1.38 999.10 90.83 68 14.4 14.90 0.211.43 1013.50 92.14 69 12.2 14.98 0.39 2.63 1025.70 93.25 70 9.9 14.990.71 4.78 1035.60 94.15 71 5.7 14.67 1.29 8.78 1041.30 94.66 72 5.214.53 1.70 11.68 1046.50 95.14

[0133] It is thus learned that the hole (5 c) in the bottom surface ofthe medicine storage unit (5) plays an important role for achieving theuniformity in the spraying amount maintaining reproduceability.

[Examples 2 to 4 and Comparative Example 3]

[0134] In Examples 2 to 4, the administering devices were produced inthe same manner as in Example 1 but forming the device body (1) and themedicine guiding unit (2) by molding polycarbonate Example 2), ABS(Example 3) and high-impact polystyrene (Example 4). In ComparativeExample 3, the administering device was produced in the same manner asin Example 1 but forming the main body (1) and the medicine guiding unit(2) by molding a polyethylene. These four kinds of administering deviceswere tested in the same manner as described in Comparative Example 1.Comparative Example 2 exhibited the same results as those of ComparativeExample 1, and Examples 2 to 4 exhibited nearly the same results asthose of Example 1.

[Examples 5, 6 and Comparative Examples 4, 5]

[0135] The administering devices of Examples 5 and 6 in which the anglea was changed from 0 degree to 50 degree while maintaining the angles βand γ at 35 and 40 degrees, and the administering devices of ComparativeExamples 4 and 5 (see Table 2) were subjected to the same spraying testas that of Example 1. The results were as shown in Table 2. It waslearned that favorable spraying performance was exhibited when the angleα lies within a range of from 15 to 45 degrees.

[0136] Table 2: Effect of the medicine guiding units having dissimilarangles α upon the powdered medicine spraying performance. TABLE 2 Ave.Angle Angle Angle spraying Corresponding α β γ amount CV* figure (°) (°)(°) (mg) (%) Max. Min. Ex. 1 30 35 40 16.7 2.2 17.1 14.8 Ex. 5 15 35 4016.9 2.8 17.4 14.7 Ex. 6 45 35 40 16.8 2.5 17.5 15.0 Comp. Ex. 4 0 35 4015.88 8.7 17.5 11.3 Comp. Ex. 5 50 35 40 14.9 7.5 18.0 10.3

[Examples 7 to 9 and Comparative Examples 6 to 8]

[0137] The administering devices of Examples 7 to 9 in which the anglesβ and γ were changed from 15 degrees to 90 degrees while maintaining theangle α at 30 degrees, and the administering devices of Control Examples6 to 8 (see Table 3) were measured for their amounts sprayed in one timeof administering operation and particle size distributions of thepowdered medicine sprayed through the spray port (2 h) by using a laserdiffraction particle size distribution measuring instrument to measuresegments (cohered masses) of particle diameters of not smaller than 300microns. The results were as shown in Table 3. In Comparative Examples 6and 8, the spraying amounts were decreased and in Comparative Example 7,the dispersing property of the particles was deteriorated.

[0138] Table 3: Effect of the medicine guiding units having dissimilarangles β and γ upon the powdered medicine dispersing performance. TABLE3 Ave. Segments Corre- Angle Angle Angle spraying larger than sponding αβ γ amount 300 μm figure (°) (°) (°) (mg) (%) Ex. 1 30 35 40 16.7 5.0Ex. 7 30 60 60 16.8 7.0 Ex. 8 30 20 20 16.6 4.7 Ex. 9 30 70 70 16.8 6.8Comp. 30 90 90 13.0 7.3 Ex. 6 Comp. 30 75 75 16.8 13.2 Ex. 7 Comp. 30 1515 13.5 7.8 Ex. 8

[Examples 10 to 13]

[0139] Controlling the unit-dose spraying amount by forming dents andprotuberances in the filter (6).

[0140] A filter A having a volume of 0.00335 cm³ on the front side(convex surface) and having a flat back surface (without a recess or aprotuberance) and a filter B having a volume of 0.00670 cm³on the frontside (convex surface) and having a volume of 0.00335 cm³ on the backsurface (concave surface) were adhered on their front surfaces and backsurfaces to the medicine multi-dose administering devices of theinvention having a medicine container chamber (5 b) of a volume of 0.314cm³, and the powdered medicine spraying testing was conducted. That is,when the front surface of the filter A faced the medicine containerchamber (5 b)(Example 10), the volume of the medicine container chamberwas 0.0314-0.00335=0.02805 cm³. Similarly, when the back surface of thefilter A faced the medicine container chamber (5 b)(Example 11), thevolume of the container was 0.0314 cm³, when the surface of the filter Bfaced the medicine container chamber (5 b)(Example 12), the volume ofthe container chamber was 0.02470 cm³, and when the back surface of thefilter B faced the medicine container chamber (5 b)(Example 13), thevolume of the container chamber was 0.03475 cm³.

[0141] In these cases, the medicine storage chambers were each filledwith 650 mg of the powdered medicine. The powdered medicine was sprayedwith n=6. The average spraying amounts and CV% were as shown in Table 4.

[0142] Table 4: Average spraying amounts and CV% depending upon dentsand protuberances of the filter (6). TABLE 4 Powder 88041 88042 880518A121 8A151 96281 lot No. Low bulk 0.456 0.441 0.493 0.441 0.525 0.442density High bulk 0.570 0.553 0.606 0.555 0.645 0.553 density Ex. 1013.38  12.60  12.98  12.94  13.52  10.56  (0.25%) (1.34%) (0.98%)(2.72%) (1.48%) (1.91%) Ex. 11 15.12  14.72  15.82  14.92  16.44  13.56 (2.11%) (0.92%) (1.48%) (1.86%) (2.25%) (1.72%) Ex. 12 9.76  9.82 10.44  10.26  10.70  8.16  (0.85%) (1.43%) (2.19%) (3.12%) (2.53%)(1.83%) Ex. 13 16.74  16.26  16.92  16.70  18.30  15.42  (0.91%) (1.88%)(1.41%) (2.36%) (0.81%) (1.92%)

1. A powdered medicine multi-dose administering device comprising: meansfor defining a medicine storage chamber (5 a) capable of storing amulti-dose amount of powdered medicine; a medicine container unit (5 b)provided under the bottom surface of said medicine storage chamber (5 a)and is capable of containing a single-dose amount of powdered medicine;a medicine guiding unit (2) capable of moving between a filling positionand an administering position while remaining in contact with the bottomsurface of said medicine storage chamber (5 a), and, when moved to thefilling position, causes said medicine container unit (5 b) to be openedto said medicine storage chamber (5 a) through opening means (2 f) and,when moved to the administering position, causes said medicine containerunit (5 b) to be closed with respect to said medicine storage chamber (5a) and causes said medicine container unit (5 b) to be communicated withthe exterior of the device through a pipe (2 g, 2 d); means (13)communicated with a hole (5 c) formed in the bottom surface of saidmedicine storage chamber (5 a) and moves said medicine guiding unit (2)between the filling position and the administering position; and a pumpunit (3) capable of blowing the air into said medicine container unit (5b) through a filter (6 a) provided in the bottom of said medicinecontainer unit (5 b); wherein said medicine guiding unit (2), at thefilling position, enables said medicine container unit (5 b) to befilled with the powdered medicine from said medicine storage chamber (5a) through said opening means and, at this moment, said hole (5 c) islocated at a position where said pump unit (3) is communicated with theexterior through said pipe (2 g, 2 d); and said medicine guiding unit(2), at the administering position, permits the powdery medicine in saidmedicine container unit (5 b) to be injected out of the device togetherwith the air through said pipe (2 g, 2 d) while closing said hole (5 c)without joining it to said opening means (2 f).
 2. A powdered medicinemulti-dose administering device according to claim 1, wherein saidmedicine storage chamber (5 a) and said medicine container unit (5 b)are molded integrally together by using a resin to define a body of thedevice (1).
 3. A powdered medicine multi-dose administering deviceaccording to claim 1, wherein said medicine guiding unit (2) includes alower disk-like portion and a pole-like portion extending upward fromthe disk-like portion, which are integrally molded together using aresin, said opening means (2 f) is so formed as to penetrate verticallythrough the disk-like portion, and said pipe (2 g, 2 d) is opened at itsone end in the lower surface (2 e) of the disk-like portion and isopened at its other end in the upper end of the pole-like portion.
 4. Apowdered medicine multi-dose administering device according to claim 3,wherein said device body (1) is nearly of a cylindrical shape, thedisk-like portion of said medicine guiding unit (2) has a diametersmaller than the inner diameter of the medicine storage chamber (5 a) ofsaid device body, and the medicine guiding unit (2) is allowed to rotatebetween the filling position and the administering position over apredetermined angular range.
 5. A powdered medicine multi-doseadministering device according to claim 1, wherein said device body (1)has a closure unit (4) on the medicine storage unit (5 a), said closureunit has a shaft hole (11) at the center thereof for passing through thepole-like portion of said medicine guiding unit (2), and said medicinestorage chamber (5 a) is sealed with said the closure unit, saidmedicine storage unit (5 a) and said medicine guiding unit (2).
 6. Apowdered medicine multi-dose administering device according to claim 5,wherein said bottom surface (2 e) of the disk-like portion of saidmedicine guiding unit (2) comes in contact with the bottom surface ofsaid medicine storage chamber (5 a), the upper and lower positions ofsaid medicine guiding unit (2) are limited by a contact portion (10)formed on said pole-like portion so as to come into contact with theinner surface of the closure unit (4), and the bottom surface (2 e) ofthe disk-like portion of said medicine guiding unit (2) is brought intointimate contact with the bottom surface of said medicine storagechamber (5 a).
 7. A powdered medicine multi-dose administering deviceaccording to claim 6, wherein said medicine guiding unit (2) has a shaft(2 j) of a circular shape in cross section formed in the upper part ofsaid junction portion (10) of the pole-like portion so as to be fittedto the shaft hole of said closure unit (4), and has a shaft (2 k) of anon-circular shape in cross section formed in the upper part thereof,the means operated from the outer side of the device to move themedicine guiding unit (2) between the filling position and theadministering position, is a rotary spray metering change-over device(13) which has a non-circular hole (13 c) that fits to the shaft (2 k)of a non-circular shape in cross section of the pole portion of saidmedicine guiding unit (2), and said medicine guiding unit (2) movesbetween the filling position and the administering position beinginterlocked to the rotational operation of said change-over device (13).8. A powdered medicine multi-dose administering device according toclaim 7, wherein the shaft (2 k) having the non-circular shape in crosssection and the non-circular hole (13 c) fitted thereby, have a homebase-like pentagonal shape in cross section.
 9. A powdered medicinemulti-dose administering device according to claim 7, wherein saidrotary spray metering change-over device (13) includes a cylindricalportion (13 a) having a large diameter and a cylindrical portion (13 b)having a small diameter, that are molded integrally together using aresin, the outer periphery of the cylindrical portion having a largediameter forms a rotary operation portion, and the cylindrical portionof a small diameter defines a powdered medicine passage (2 c) formedtherein, has the non-circular hole (13 c) formed in the base portion,and defines a spray port in an end (2 h) thereof.
 10. A powderedmedicine multi-dose administering device according to claim 7, whereinsaid rotary spray metering change-over device (13) is formed to bedetachable from said device body (1) and said medicine guiding unit (2).11. A powdered medicine multi-dose administering device according toclaim 3, wherein a central hole (14) is formed at the center in thebottom surface (2 e) of the disk-like portion of said medicine guidingunit (2), and a protuberance (8) is formed at the center on the bottomsurface of said medicine storage chamber (5 a) to work as a shaft thatfits to the central hole (14) in order to stabilize the turning of saidmedicine guiding unit (2).
 12. A powdered medicine multi-doseadministering device according to claim 4, wherein said rotary spraymetering change-over device (13) has an arcuate groove (13 d) formed inthe upper surface of said cylindrical portion (13 a) of the largediameter with said non-circular hole (13 c) as a center, said closureunit (4) has a protuberance (4 a) formed on the upper surface thereof soas to be inserted in said arcuate groove (13 d) thereby to limit therotation of said medicine guiding unit (2) and of said rotary spraymetering change-over device(13), wherein, when said protuberance (4 a)is located at an end of said arcuate groove (13 d), the position forfilling the powdered medicine is limited and, when said protuberance (4a) is located at the other end, the position for administering thepowdered medicine is limited.
 13. A powdered medicine multi-doseadministering device according to claim 4, wherein an angle (x)subtended by the center of said opening means (2 f) and the center ofthe opening of said pipe (2 g) on the bottom surface of the disk-likeportion of said medicine guiding unit (2), is equal to, or is slightlysmaller than, an angle (y) subtended by one end and other end of thearcuate groove (13 d) in the upper surface of the cylindrical portion(13 a) of the large diameter from the center of said non-circular hole(13 c) of said rotary spray metering change-over device (13)(x≦y), andis from 60 degrees to 180 degrees.
 14. A powdered medicine multi-doseadministering device according to claim 2, wherein the disk-like portionof said medicine guiding unit (2) on the side of the medicine storagechamber (5 a) is inclined upward from the periphery toward the center atan angle (a) in a range of from 15 degrees to 45 degrees with respect tothe bottom surface (2 e) of the disk-like portion.
 15. A powderedmedicine multi-dose administering device according to claim 2, whereinsaid pipe (2 g) provided in the medicine guiding unit (2) is inclinedupward at angles (β, γ) in a range of from 20 degrees to 70 degrees withrespect to the bottom surface (2 e) of said medicine guiding unit (2).16. A powdered medicine multi-dose administering device according toclaim 1, wherein said opening means (2 f) in said medicine guiding unit(2) is a hole (2 f) penetrating vertically through the disk-likeportion.
 17. A powdered medicine multi-dose administering deviceaccording to claim 16, wherein said opening means (2 f) extends upwardfrom the opening in the bottom surface (2 e) of the disk-like portion,and forms a pocket-like dent (2 m) on the side facing said medicinestorage chamber (5 a), said dent (2 m) assisting a smooth conveyance ofthe powdered medicine in the medicine storage chamber (5 a) into themedicine container chamber (5 b) during the operation for changing overthe filling and administering.
 18. A powdered medicine multi-doseadministering device according to claim 4, wherein one or plural piecesof vanes (21) are formed on the outer side of said pole-like portion ofsaid medicine guiding unit (2), so that the powdered medicine in themedicine storage chamber (5 a) is stirred as the medicine guiding unit(2) moves between the filling position and the administering position.19. A powdered medicine multi-dose administering device according toclaim 1, wherein said pump unit (3) is at least partly constituted by aflexible resin so as to define an air chamber therein, the openingportion of said pump unit (3) is coupled to the lower part of the devicebody (1), the pump unit (3) is depressed and relaxed to blow the airinto said medicine container chamber (5 b) through said filter (6) inthe air chamber, and the powdered medicine is blown out of the devicethrough said pipe (2 g, 2 d, 2 c).
 20. A powdered medicine multi-doseadministering device according to claim 1, wherein said filter (6) has arecessed portion or a protruded portion on the side facing said medicinecontainer chamber (5 b) to adjust the volume of said medicine containerchamber (5 b).
 21. A powdered medicine multi-dose administering deviceaccording to claim 1, wherein said medicine guiding unit (2) is obtainedby molding one or more kinds of high-molecular materials selected fromthe group consisting of a polycarbonate, ABS, a high-impact polystyreneand a cyclic olefin copolymer.
 22. A powdered medicine multi-doseadministering device according to claim 1, wherein a drying agent ismounted on a portion of the device.
 23. A powdered medicine multi-doseadministering device according to claim 1, wherein said powderedmedicine multi-dose administering device is disposable.
 24. A powderedmedicine multi-dose administering device according to claim 1, whereinsaid powdered medicine multi-dose administering device is foradministering the medicine into the body cavity.
 25. A powdered medicinemulti-dose administering device according to claim 1, wherein saidpowdered medicine multi-dose administering device is for administeringthe medicine into the nasal cavity.
 26. A powdered medicine multi-doseadministering device according to claim 1, wherein said powderedmedicine multi-dose administering device is for administering themedicine into the lung.
 27. A powdered medicine multi-dose administeringmethod, wherein a medicine container unit (5 b) capable of containing apowdered medicine of a unit-dose amount is provided under the bottomsurface of a medicine storage chamber (5 a) capable of storing thepowdered medicine of an amount of many times of administering operation,a medicine guiding unit (2) is provided to move between a fillingposition and an administering position while maintaining a contact withthe bottom surface of said medicine storage chamber (5 a) so that, whenmoved to the filling position, said medicine container unit (5 b) isopened to said medicine storage chamber (5 a) through opening means (2f) and, when moved to the administering position, said medicinecontainer chamber (5 b) is closed with respect to said medicine storagechamber (5 a) and is communicated with the exterior of the devicethrough a pipe (2 g, 2 d), and a hole (5 c) is formed in the bottomsurface of said medicine storage chamber (5 a); said medicine guidingunit (2) is moved between the filling position and the administeringposition, so that: at the filling position, said medicine container unit(5 b) is filled with the powdered medicine from said medicine storagechamber (5 a) through said opening means and, at the same time, saidhole (2 c) is pneumatically connected to the pump unit (3) through saidpipe (2 g, 2 d); the powdered medicine in said medicine container unit(5 b) is swept and metered into an amount of one time of administeringoperation as said medicine guiding unit moves from the filling positionto the administering position; and at the administering position, thepump (3) is operated to blow the air into said medicine container unit(5 b) through the filter (6) to inject the powdered medicine out of thedevice through said pipe (2 g, 2 d, 2 c).